Deeg M A, Bowen R F, Williams M D, Olson L K, Kirk E A, LeBoeuf R C
Department of Medicine, Indiana University School of Medicine and the Richard L. Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana 46202, USA.
Am J Physiol Endocrinol Metab. 2001 Jul;281(1):E147-54. doi: 10.1152/ajpendo.2001.281.1.E147.
Glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) is a high-density lipoprotein-associated protein. However, the tissue source(s) for circulating GPI-PLD and whether serum levels are regulated are unknown. Because the diabetic state alters lipoprotein metabolism, and liver and pancreatic islets are possible sources of GPI-PLD, we hypothesized that GPI-PLD levels would be altered in diabetes. GPI-PLD serum activity and liver mRNA were examined in two mouse models of type 1 diabetes, a nonobese diabetic (NOD) mouse model and low-dose streptozotocin-induced diabetes in CD-1 mice. With the onset of hyperglycemia (2- to 5-fold increase over nondiabetic levels), GPI-PLD serum activity and liver mRNA increased 2- to 4-fold in both models. Conversely, islet expression of GPI-PLD was absent as determined by immunofluorescence. Insulin may regulate GPI-PLD expression, because insulin treatment of diabetic NOD mice corrected the hyperglycemia along with reducing serum GPI-PLD activity and liver mRNA. Our data demonstrate that serum GPI-PLD levels are altered in the diabetic state and are consistent with liver as a contributor to circulating GPI-PLD.
糖基磷脂酰肌醇特异性磷脂酶D（GPI-PLD）是一种与高密度脂蛋白相关的蛋白质。然而，循环GPI-PLD的组织来源以及血清水平是否受到调节尚不清楚。由于糖尿病状态会改变脂蛋白代谢，且肝脏和胰岛可能是GPI-PLD的来源，我们推测糖尿病患者的GPI-PLD水平会发生改变。在两种1型糖尿病小鼠模型中检测了GPI-PLD的血清活性和肝脏mRNA，一种是非肥胖糖尿病（NOD）小鼠模型，另一种是低剂量链脲佐菌素诱导的CD-1小鼠糖尿病模型。随着高血糖的出现（比非糖尿病水平增加2至5倍），两种模型中GPI-PLD的血清活性和肝脏mRNA均增加了2至4倍。相反，通过免疫荧光测定，胰岛中未检测到GPI-PLD的表达。胰岛素可能调节GPI-PLD的表达，因为用胰岛素治疗糖尿病NOD小鼠可纠正高血糖，同时降低血清GPI-PLD活性和肝脏mRNA。我们的数据表明，糖尿病状态下血清GPI-PLD水平会发生改变，且与肝脏是循环GPI-PLD的来源之一相一致。
